tbuckley/cabot-search huggingface dataset:
Lung cancer risk prediction nomogram in Chinese female non-smokers.
Authors: Guo Lan-Wei
Journal: Journal of Clinical Oncology (2022)

10530 Background: About 53% of lung cancers in females are not attributable to smoking worldwide. The aim was to develop and validate a simple and non-invasive model which could assess and stratify lung cancer risk in female non-smokers in China. Methods: A large-sample size, population-based study was conducted under the framework of a population-based Cancer Screening Program in Urban China (CanSPUC). Data on the lung cancer screening in Henan province, China, from October 2013 to October 2019 were used and randomly divided into the training and validation sets. Related risk factors were identified through multivariable Cox regression analysis, followed by establishment of risk prediction nomogram. Discrimination [area under the curve (AUC)] and calibration were further performed to assess the validation of risk prediction nomogram in the training set, and then validated by the validation set. Results: A total of 151,834 eligible subjects were included, with a mean age of 55.34 years. Subjects were randomly divided into the training (75,917) and validation (75,917) sets. Elder age, history of chronic respiratory disease, first-degree family history of lung cancer, menopause, and history of benign breast disease were the independent risk factors for lung cancer. Using these five variables, we plotted 1-year, 3-year, and 5-year lung cancer risk prediction nomogram. The AUC was 0.762, 0.718, and 0.703 for the 1-, 3- and 5-year lung cancer risk in the training set, respectively. In the validation set, the model showed a good predictive discrimination, with the AUC was 0.646, 0.658, and 0.650 for the 1-, 3- and 5-year lung cancer risk. Conclusions: We developed and validated a simple and non-invasive lung cancer risk model in female non-smokers. This model can be applied to identify and triage patients at high risk for developing lung cancers in female non-smokers.
Acute kidney injury after mini and standard percutaneous nephrolithotomy: Pattern of presentation and predictors
Authors: U.G. Falagario, A. Mangiatordi, A. Ricapito, M. Auciello, S.M. Bruno, G.M. Busetto, C. Bettocchi, G. Carrieri, L. Cormio
Journal: European Urology (2022)
Nivolumab (NIVO) plus chemotherapy (chemo) or ipilimumab (IPI) versus chemo as first-line (1L) treatment for advanced esophageal squamous cell carcinoma (ESCC): Expanded efficacy and safety analyses from CheckMate 648.
Authors: Ian Chau, Jaffer A. Ajani, Yuichiro Doki, Jianming Xu, Lucjan Wyrwicz, Satoru Motoyama, Takashi Ogata, Hisato Kawakami, Chih-Hung Hsu, Antoine Adenis, Farid El Hajbi, Maria Di Bartolomeo, Maria Ignez Freitas Melro Braghiroli, Eva Holtved, Mariela A. Blum Murphy, Sandzhar Abdullaev, Samira Soleymani, Ming Lei, Ken Kato, Yuko Kitagawa
Journal: Journal of Clinical Oncology (2022)

4035 Background: NIVO + chemo and NIVO + IPI demonstrated significant overall survival (OS) benefit vs chemo in previously untreated patients (pts) with advanced ESCC in the phase 3 CheckMate 648 study. We report expanded results from the primary analysis with 13-month (mo) minimum follow-up. Methods: Pts with previously untreated, unresectable advanced, recurrent, or metastatic ESCC were randomized to NIVO (240 mg Q2W) + chemo (fluorouracil + cisplatin Q4W), NIVO (3 mg/kg Q2W) + IPI (1 mg/kg Q6W), or chemo. Primary endpoints were OS and progression-free survival (PFS) per blinded independent central review (BICR) in pts with tumor cell programmed death ligand 1 (PD-L1) ≥ 1%. Secondary endpoints planned for hierarchical testing included OS, PFS, and objective response rate (ORR) per BICR in all randomized pts. Duration of response (DOR) per BICR and PFS2 per investigator (time from randomization to progression after subsequent systemic therapy, initiation of second subsequent systemic therapy, or death) were exploratory endpoints. Results: Among all pts randomized to NIVO + chemo (n = 321), NIVO + IPI (n = 325), or chemo (n = 324), PFS2 favored NIVO + chemo (HR 0.64, 95% CI 0.54–0.77) and NIVO + IPI (HR 0.74, 95% CI 0.62–0.88) vs chemo. ORR (95% CI) was 47% (42–53), 28% (23–33), and 27% (22–32), respectively. More responders with NIVO + chemo or NIVO + IPI vs chemo had prolonged DOR (≥12 mo; 39%, 48%, and 23%, respectively). Efficacy data by tumor cell PD-L1 and PD-L1 combined positive score will be presented. Grade 3/4 treatment-related adverse events with potential immunologic etiology (select TRAEs) occurred in ≤ 6% of pts with NIVO + chemo and NIVO + IPI, and non-endocrine select TRAEs resolved in 57%–95% of pts across organ categories (Table). Conclusions: NIVO + chemo and NIVO + IPI demonstrated favorable PFS2 and a higher proportion of pts with prolonged DOR vs chemo, as well as acceptable safety profiles. These results provide further support for each regimen as a new potential 1L standard of care in advanced ESCC. Clinical trial information: NCT03143153. [Table: see text]
QOL-17. Neurocognitive outcomes after treatment for medulloblastoma with reduced primary site target volume margins
Authors: Trisha Larkin, Tong Lin, Jason M Ashford, Arzu Onar-Thomas, Amar Gajjar, Heather M Conklin, Thomas Merchant
Journal: Neuro-Oncology (2022)

Abstract PURPOSE: Children treated for medulloblastoma (MB) undergo intensive multimodality treatment compromising surgery, irradiation, and chemotherapy, which is associated with a significant risk of neurocognitive deficits. Successive multicenter frontline treatment protocols have introduced reduced posterior fossa boost margins for cranial irradiation for sparing collateral tissue and preserving function. This study examines neurocognitive outcomes in the setting of reduced primary site target volume margins in children treated for MB. PATIENTS &amp; METHODS: Prospective longitudinal neurocognitive data were collected from newly diagnosed patients with MB (n = 372, ages 3-21 years) enrolled on one of two sequential multicenter clinical protocols between 1996 and 2012. The treatment regimen included surgery, risk-adapted craniospinal irradiation with a posterior fossa boost with restricted clinical target volume (CTV) margins (2 cm and 1 cm), and dose-intensive chemotherapy. Comparative analysis of neurocognitive outcomes was performed using linear mixed-effects models. RESULTS: Intelligence quotient (IQ) scores were better preserved in average-risk patients who received treatment using a clinical target volume with a lesser margin of 1 cm (p &amp;lt; 0.0099). Findings were consistent with prior studies on measures of academics including reading performance, mathematical reasoning, and spelling across both risk groups regardless of CTV. CONCLUSION: This study presents compelling evidence in favor of restricted CTVs for preserving IQ without sacrificing treatment efficacy in average childhood MBs.
Subgroup analysis in RE-MIND2, an observational, retrospective cohort study of tafasitamab plus lenalidomide versus systemic therapies in patients with relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL).
Authors: Grzegorz S. Nowakowski, Dok Hyun Yoon, Erel Joffe, Pier Luigi Zinzani, Lorenzo Sabatelli, Eva E. Waltl, Carmelita G. Alvero, Georg Hess, Peter A. Riedell, Kibum Kim, Diana Brixner, Gilles A. Salles
Journal: Journal of Clinical Oncology (2022)

7560 Background: Tafasitamab (tafa) + lenalidomide (LEN) demonstrated efficacy in adult patients (pts) with R/R DLBCL ineligible for autologous stem-cell transplant in the pivotal Phase II study L-MIND (NCT02399085) and received accelerated approval in the United States in 2020 and conditional marketing authorization in Europe and Canada in 2021 in this setting. RE-MIND2 (NCT04697160), an observational, retrospective cohort study, compared pt outcomes from L-MIND with matched pt cohorts treated with other NCCN/ESMO recommended therapies. Methods: Methodology for RE-MIND2 has been presented previously. Hypothesis-generating analyses were conducted for pt subgroups of number of extranodal sites (ENS) (0–1 vs ≥2) and elevated lactate dehydrogenase (LDH) (yes vs no) in matched cohorts of pts receiving tafa + LEN vs systemic therapies pooled (STP), polatuzumab vedotin + bendamustine + rituximab (pola-BR), rituximab + LEN (R2), and CD19 CAR-T therapies (CAR-T). The primary endpoint was overall survival (OS). Results: Of 3,454 pts enrolled, 961, 106, 106, and 149 were treated with STP, pola-BR, R2, and CAR-T, resulting in 76, 24, 33, and 37 matched pairs for pts receiving tafa + LEN, respectively. Hazard ratios (HR) for OS show a trend toward favoring tafa + LEN in most pt subgroups (Table). Conclusion: These analyses suggest that tafa + LEN may be associated with improved OS vs selected systemic therapies for certain pts with high-risk disease and may further inform physicians’ treatment choices for pts with R/R DLBCL. These analyses are not powered for statistical comparison; small sample sizes in some subgroups result in wide confidence intervals (CI) and so results must be interpreted with caution. Data for other treatment cohorts, pt subgroups, and endpoints will be presented. Funding: MorphoSys AG. Clinical trial information: NCT04697160. [Table: see text]
Diagnosis of malnutrition according to glim criteria predicts complications and six-month survival in cancer outpatients.
Authors: Maria Marti Pi, Marta Gascon Ruiz, Diego Casas-Deza, Irene Torres Ramon, Maria Zapata-Garcia, Andrea Sesma, Julio Jose Lambea- Sorrosal, Maria Alvarez, Elisa Quilez, Maria Zurera Berjaga, Alba Moratiel Pellitero, Ines Ruiz Moreno, Ana Goas Gomez, Dolores Isla, José Miguel Arbonés-Mainar
Journal: Journal of Clinical Oncology (2022)

e24093 Background: Malnutrition is a condition with great impact in oncology patients. Poor nutritional status is often associated with increased morbidity and mortality, increased toxicity and reduced tolerance to chemotherapy, among other complications. The recent GLIM criteria for malnutrition aim to homogenize its diagnosis, considering the baseline disease status. Due to the few studies that assess the predictive capacity of these new criteria, we aimed to evaluate their performance for the prediction of complications and mortality in patients with cancer. Methods: Prospective, single-centre study. All outpatients under active treatment for head and neck, upper gastrointestinal and colorectal tumors between February and October 2020 were recruited. These patients were followed up for 6 months, assessing the occurrence of complications and survival, based on GLIM diagnosis of malnutrition. Results: We enrolled 165 outpatients 46.66% malnutrition. During 6-month follow-up, patients with malnutrition (46.7%, according to GLIM criteria) had an ̃3-fold increased risk of hospital admission (p &lt; 0.001) and the occurrence of severe infections (considered as such those requiring hospitalization, intravenous antibiotics and/or drainage by interventional procedure) during follow-up (p = 0.002). Similarly, malnourished patients had a 3.5-fold increased risk of poor pain control and a 4.4-fold increased need for a higher dose of opioids (both p &lt; 0.001). They also had a 2.6-fold increased risk of toxicity (p = 0.044) and a 2.5-fold increased likelihood of needing a dose decrease or discontinuation of cancer treatment (p = 0.011). 6-month survival of malnourished patients was significantly lower (p = 0.023) than non-malnourished patients. Conclusions: Diagnosis of malnutrition according to GLIM criteria in oncology patients on active treatment predicts increased complications and worse survival at 6-month follow-up, making them a useful tool to assess the nutritional status of oncology patients.[Table: see text]
Four-Octyl itaconate ameliorates periodontal destruction via Nrf2-dependent antioxidant system
Authors: Liangjing Xin, Fuyuan Zhou, Chuangwei Zhang, Wenjie Zhong, Shihan Xu, Xuan Jing, Dong Wang, Si Wang, Tao Chen, Jinlin Song
Journal: International Journal of Oral Science (2022)

Abstract Periodontitis is a widespread oral disease characterized by continuous inflammation of the periodontal tissue and an irreversible alveolar bone loss, which eventually leads to tooth loss. Four-octyl itaconate (4-OI) is a cell-permeable itaconate derivative and has been recognized as a promising therapeutic target for the treatment of inflammatory diseases. Here, we explored, for the first time, the protective effect of 4-OI on inhibiting periodontal destruction, ameliorating local inflammation, and the underlying mechanism in periodontitis. Here we showed that 4-OI treatment ameliorates inflammation induced by lipopolysaccharide in the periodontal microenvironment. 4-OI can also significantly alleviate inflammation and alveolar bone loss via Nrf2 activation as observed on samples from experimental periodontitis in the C57BL/6 mice. This was further confirmed as silencing Nrf2 blocked the antioxidant effect of 4-OI by downregulating the expression of downstream antioxidant enzymes. Additionally, molecular docking simulation indicated the possible mechanism under Nrf2 activation. Also, in Nrf2 −/− mice, 4-OI treatment did not protect against alveolar bone dysfunction due to induced periodontitis, which underlined the importance of the Nrf2 in 4-OI mediated periodontitis treatment. Our results indicated that 4-OI attenuates inflammation and oxidative stress via disassociation of KEAP1-Nrf2 and activation of Nrf2 signaling cascade. Taken together, local administration of 4-OI offers clinical potential to inhibit periodontal destruction, ameliorate local inflammation for more predictable periodontitis.
Single cell profiling of adipose tissue in atherosclerosis
Authors: U Thanigai Arasu, T Ord, J Liikkanen, S Kettunen, T Lonnberg, S Palani, S Yla-Herttuala, A Roivainen, MU Kaikkonen
Journal: Cardiovascular Research (2022)

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): Academy of Finland Sigrid Jusélius Foundation Adipose tissue influences the physiological and pathological processes in our body by regulating lipid storage and metabolic homeostasis. Extracellular matrix (ECM) is a dynamic and complex assemblage consisting of polysaccharides, proteogylcans and signalling proteins. Though both adipocytes and non- adipose cells of the stromal fraction contribute to ECM maintenance, role of adipose tissue ECM in the disease remains poorly characterised. High fat diet (HFD) and obesity represent major risk factors for atherosclerosis. Our overall aim in this study was to understand HFD induced changes in the adipose tissue during atherosclerosis progression using single cell RNA sequencing (scRNA-seq), to identify the ligands responsible for changes in the expression of ECM components and to characterise the role of ECM protein fibrillin in disease associated tissue changes. We performed scRNA-seq in the adipose tissue of control mice and atherosclerotic LDLR-/- / ApoB100/100 subjected to 1 (early disease) or 3 months (advanced disease) of HFD. This allowed us to identify 13 different cell types in the adipose tissue of the diseased mice. Among them, we identified mesenchymal cells (MSC) undergoing changes from putatively adipogenic to fibrogenic cells. The differentially expressed genes in the MSC population exhibited functions related to ECM development, maintenance and signalling. We identified Fibrillin-1 (Fbn1) as one of the most prominent up regulated genes and studied the effect of Fbn1 knockout in ApoE-/- Fbn1C1039G+/- mice. The Fbn1 knockout mice model suited our experimental design to study the adipose tissue during atherosclerosis as the mice developed significantly large and unstable plaques characterised by large necrotic core. Our results demonstrated that adipose tissue expresses a new subtype with HFD in Fbn1 knockout mice, which could be associated with insulin resistance and fat accumulation. Fbn1 knockout led to an altered phenotype of MSCs (or adipocytes) in adipose tissue. Altogether, our analysis provides the first steps toward understanding the role of MSCs in ECM-related changes during atherosclerosis and HFD stimulation.
Development and validation of a deep learning system for sound-based prediction of urinary flow
Authors: H.J. Lee, E. Aslim, B. Balamurali, L.Y.S. Ng, T. Kuo, K.S. Lim, C. Lin, C.J. Clarke, P. Privasarshinee, J. Jer-Ming, L.G. Ng
Journal: European Urology (2022)
Levering internet-based discussion data from gynecological cancer survivors to inform survivorship care: A mixed methods thematic analysis approach.
Authors: Elizabeth Adams, David Tallman, Marcy Haynam, Larissa Nekhlyudov, Maryam B. Lustberg
Journal: Journal of Clinical Oncology (2022)

e24143 Background: Internet and social media platforms offer insight into the experience of survivorship, but the volume of narrative data is often cumbersome for thorough thematic analysis. We present a semi-automated mixed methods approach to analyze web-based discussions and demonstrate its utility on American Cancer Society (ACS) Discussion Board posts from gynecologic cancer survivors. Methods: Posts from the ACS Ovarian Cancer, Uterine Cancer, and Other Gynecological Cancer Discussion Boards were analyzed for psychosocial themes described in the Cancer Survivorship Care Framework. Quantitative analysis was facilitated by verified keywords created for each theme of interest and was completed via custom Python scripts and R packages. Qualitative analysis was expedited by theme keywords and completed on a subset of posts. Results: A total of 125,498 posts made by 6,436 gynecological cancer survivors and caregivers between July 2000 and February 2020 were evaluated. Of all posts, 23,458 were related to psychosocial aspects of survivorship and were analyzed. Quantitative analysis revealed that survivors frequently discussed the role of friends and family in care, fatigue, health insurance issues, and the effect of cancer on loved ones. The most frequently used psychosocial-related words were “family,” “hope,” and “help.” Qualitative analysis demonstrated that survivors frequently discussed coping and caregiver relationships, where survivors sought advice on topics including spousal emotional adjustment, financial toxicity, and confronting mortality. Conclusions: Online platforms offer great opportunity to learn about patient experiences of survivorship care. Candid conversations between survivors may be leveraged to inform survivorship practices and improve future survivorship initiatives. Our novel methodology expedites thematic analysis of such robust narrative data and its translation into survivorship settings.
MicroRNA biomarkers of platelet function
Authors: C Gutmann, T Barwari, C Schulte, B Singh, K Theofilatos, A Joshi, A Zampetaki, M Chan, P Armstrong, S Kiechl, J Willeit, T Warner, M Mayr
Journal: Cardiovascular Research (2022)

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): British Heart Foundation (BHF), VASCage (Centre for Promoting Vascular Health in the Ageing Community) of the Austrian Research Promotion Agency FFG (COMET program - Competence Centers for Excellent Technologies) Introduction Antiplatelet therapy (APT) leads to reduced morbidity and mortality in patients with cardiovascular disease but some still have thrombotic events. Tailoring APT to platelet function is currently limited by a lack of suitable platelet function tests. It has been previously shown that different circulating microRNAs (miRNAs) are derived from platelets and their measurement could provide new markers of platelet reactivity. Purpose To compare the release of different platelet miRNAs in response to different platelet agonists. Methods Measurements of platelet function were performed by light transmission aggregometry (LTA) in participants of the 2015 follow-up of the Bruneck study (n=338), using the following agonists: arachidonic acid (1mM), adenosine diphosphate (5µM, 20µM), collagen (0.4 µg/ml, 4 µg/ml, 10µg/ml), TRAP-6 amide (25µM) and U46619 (10µM). LTA platelet releasates were then used for RT-qPCR measurements of five platelet-enriched miRNAs (miR-21, miR-126, miR-150, miR-197, miR-223). Platelet-poor plasma (PPP) served as negative control. Results Platelet activation led to aggregation and extracellular release of miRNAs, with aspirin users (n=155) showing significantly lower miRNA release than non-aspirin users (n=183). Agonist responsiveness differed among miRNAs, with miR-21 being hyperresponsive to arachidonic acid and miR-150 being hyperresponsive to adenosine diphosphate, whilst release of miR-126, miR-197 and miR-223 was strongest to collagen (10µg/ml). In non-aspirin users, inflammation markers such as granulocyte counts or C-reactive protein correlated positively with platelet-derived miRNAs measured in PPP, whilst they correlated negatively with platelet-derived miRNAs measured in releasates. These effects were absent in aspirin users. Conclusions MiRNAs released from activated platelets can be reliably detected in PPP and platelet releasates. Preferential release of miRNAs in response to specific agonists suggests a selective release mechanism. Elevated PPP levels and decreased releasate levels of platelet-derived miRNAs in inflammatory environments suggest platelet exhaustion ex vivo due to platelet pre-activation.
Activated Drp1 regulates p62-mediated autophagic flux and aggravates inflammation in cerebral ischemia-reperfusion via the ROS-RIP1/RIP3-exosome axis
Authors: Xue Zeng, Yun-Dong Zhang, Rui-Yan Ma, Yuan-Jing Chen, Xin-Ming Xiang, Dong-Yao Hou, Xue-Han Li, He Huang, Tao Li, Chen-Yang Duan
Journal: Military Medical Research (2022)

Abstract Background Cerebral ischemia-reperfusion injury (CIRI) refers to a secondary brain injury that can occur when the blood supply to the ischemic brain tissue is restored. However, the mechanism underlying such injury remains elusive. Methods The 150 male C57 mice underwent middle cerebral artery occlusion (MCAO) for 1 h and reperfusion for 24 h, Among them, 50 MCAO mice were further treated with Mitochondrial division inhibitor 1 (Mdivi-1) and 50 MCAO mice were further treated with N-acetylcysteine (NAC). SH-SY5Y cells were cultured in a low-glucose culture medium for 4 h under hypoxic conditions and then transferred to normal conditions for 12 h. Then, cerebral blood flow, mitochondrial structure, mitochondrial DNA (mtDNA) copy number, intracellular and mitochondrial reactive oxygen species (ROS), autophagic flux, aggresome and exosome expression profiles, cardiac tissue structure, mitochondrial length and cristae density, mtDNA and ROS content, as well as the expression of Drp1-Ser616/Drp1, RIP1/RIP3, LC3 II/LC3 I, TNF-α, IL-1β, etc., were detected under normal or Drp1 interference conditions. Results The mtDNA content, ROS levels, and Drp1-Ser616/Drp1 were elevated by 2.2, 1.7 and 2.7 times after CIRI ( P &lt; 0.05). However, the high cytoplasmic LC3 II/I ratio and increased aggregation of p62 could be reversed by 44% and 88% by Drp1 short hairpin RNA (shRNA) ( P &lt; 0.05). The low fluorescence intensity of autophagic flux and the increased phosphorylation of RIP3 induced by CIRI could be attenuated by ROS scavenger, NAC ( P &lt; 0.05). RIP1/RIP3 inhibitor Necrostatin-1 (Nec-1) restored 75% to a low LC3 II/LC3 I ratio and enhanced 2 times to a high RFP-LC3 after Drp1 activation ( P &lt; 0.05). In addition, although CIRI-induced ROS production caused no considerable accumulation of autophagosomes ( P &gt; 0.05), it increased the packaging and extracellular secretion of exosomes containing p62 by 4 – 5 times, which could be decreased by Mdivi-1, Drp1 shRNA, and Nec-1 ( P &lt; 0.05). Furthermore, TNF-α and IL-1β increased in CIRI-derived exosomes could increase RIP3 phosphorylation in normal or oxygen–glucose deprivation/reoxygenation (OGD/R) conditions ( P &lt; 0.05). Conclusions CIRI activated Drp1 and accelerated the p62-mediated formation of autophagosomes while inhibiting the transition of autophagosomes to autolysosomes via the RIP1/RIP3 pathway activation. Undegraded autophagosomes were secreted extracellularly in the form of exosomes, leading to inflammatory cascades that further damaged mitochondria, resulting in excessive ROS generation and the blockage of autophagosome degradation, triggering a vicious cycle.